New method to improve diagnostics and treatment for corneal dystrophy

The results from a Fight for Sight funded study paves the way for early diagnosis of a corneal eye condition, as well as aiding the development of new targeted treatments.

The study published in Genetics in Medicine last week used an innovative method to sequence the gene mutation responsible for more than three quarters of cases of an eye condition called Fuchs Endothelial Corneal Dystrophy (FECD). The mutated region has not previously been sequenced accurately.

Researchers led by Dr Alice Davidson at UCL applied a new technique known as ‘No Amp Targeted Sequencing’ which enables the mutation to be accurately sequenced, for the first time in patient samples.

The sequencing technique will help the development of new treatments targeted to the mutation. The technique could also detect the condition before symptoms have begun to show, which will help identify patients suitable for preventative treatments.

Results from this study could also have wider implications for more than 40 human diseases such as Huntington’s disease, which are caused by a similar type of mutation.

Dr Neil Ebenezer, Director of Research, Policy and Innovation at Fight for Sight, said: “Currently some gene sequences are very difficult to faithfully recreate so this new technique means researchers will be able to more accurately recreate gene sequences, improve diagnosis and help develop treatments.

He added "It’s particularly exciting as this technique also has potential applications for more than forty other conditions."

Dr Alice Davidson, a Fight for Sight funded researcher from UCL Institute of Ophthalmology, said: “I am enormously excited by our application of this innovative method. The technique has already improved our understanding of Fuchs endothelial corneal dystrophy biology and hopefully, in the future, will help facilitate more effective diagnosis and treatment for patients.”

Fuchs Dystrophy is an inherited, sight threatening condition which is estimated to affect up to 4.5% of individuals over 50 years of age. The condition affects the cornea, causing light sensitivity, cloudy vision and the ability to see details clearly.

In order to identify mutations that may be disease causing, DNA from patients is amplified and then sequenced. However in some genomic regions, such as those with very high guanine-cytosine (GC) content and repetitive sequences these are difficult to faithfully amplify.

The researchers have developed a new technique that employs the CRISPR-Cas9 system to targeting multiple genetic regions. This method, in conjunction with long reads generated through Single Molecule, Real-Time (SMRT) sequencing, enables enrichment and sequencing of complex genomic regions that cannot be easily investigated with other technologies.

This work was funded by Fight for Sight, Academy of Medical Sciences Springboard Award, The National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust and UCL Institute of Ophthalmology, Rosetrees Trust, Moorfields Eye Charity, and the National Eye Research Centre.